The Role of Capillary Flow and Autoregulation in Primary Open Angle Glaucoma Project Summary This K23 application is submitted by Osamah Saeedi, MD, an Assistant Professor in the Department of Ophthalmology and Visual Sciences in the University of Maryland, Baltimore. My long-term goal is to become an independent clinical investigator focusing on the role of ocular blood flow at the capillary level in the development and progression of primary open angle glaucoma. Towards this goal, I propose a mentored career development plan that includes training in novel techniques of angiography capable of imaging erythrocyte movement and quantification of absolute blood flow; human subjects training; and the conduction of clinical trials. During the grant period I will obtain a Master's o Science in Clinical Research. Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. Although intraocular pressure (IOP) lowering remains the only proven therapy for the disease, many patients continue to experience irreversible vision loss despite effective IOP-lowering therapy. A critical need, therefore, exists to identify alternative, potentilly modifiable biomarkers for POAG. The proposed research focuses on identifying and developing sensitive imaging biomarkers as they relate to capillary erythrocyte flow. There is strong evidence for a vascular component in the development and progression of POAG. Capillary erythrocyte flow (which differs from bulk blood flow) refers to individual erythrocyte movement within the capillaries, which is closely linked to the metabolic capacity of blood circulations to support the ocular tissues. One of my mentors, Dr. Robert Flower, has developed advanced techniques to evaluate and quantify ocular blood flow at the individual capillary level, using Erythrocyte Mediated Indocyanine Green Angiography (EMA) and Fluorescent Mediated Photo-Photoplethysmography (FM-PPG). EMA permits direct observation of erythrocyte movement within the capillaries and quantification of erythrocyte velocity and motility as well as local hematocrit. FM-PPG is a method that allows for the absolute quantification of blood flow using Indocyanine Green (ICG) angiography. The overall goal of this research is to determine the role of capillary blood flow and capillary erythrocyte flow in POAG. In specific aim 1, I propose cross-sectional human studies to measure and compare erythrocyte motility, erythrocyte velocity, blood flow, and local hematocrit in patients with POAG, POAG suspects, and controls. In specific aim 2, I propose cross-sectional human studies to measure the autoregulation of these variables. I hypothesize that patients with POAG have less erythrocyte velocity and erythrocyte motility, lower blood flow, lower local hematocrit, and poorer vascular autoregulation as compared to controls. I further hypothesize that local changes in these parameters will correlate to structural and functional glaucomatous deficits, specifically retinal nerve fiber laye (RNFL) thickness and visual field deficits.